Mifeprex

SIDE EFFECTS

The treatment procedure is designed to induce the vaginal bleeding and uterine
cramping necessary to produce an abortion. Nearly all of the women who receive
Mifeprex and misoprostol will report adverse reactions, and many can be expected
to report more than one such reaction. About 90% of patients report adverse
reactions following administration of misoprostol on day three of the treatment
procedure. Those adverse events that occurred with a frequency greater than
or equal to 1% in the U.S. and French trials are shown in Table 3.

Vaginal bleeding and uterine cramping are expected consequences of the action
of Mifeprex as used in the treatment procedure. Following administration of
mifepristone and misoprostol in the French clinical studies, 80 to 90% of women
reported bleeding more heavily than they do during a heavy menstrual period
(see WARNINGS, Vaginal Bleeding). Women also typically experience abdominal
pain, including uterine cramping. Other commonly reported side effects were
nausea, vomiting and diarrhea. Some adverse reactions reported during the four
hours following administration of misoprostol were judged by women as being
more severe than others: the percentage of women who considered any particular
adverse event as severe ranged from 2 to 35% in the U.S. and French trials.
After the third day of the treatment procedure, the number of reports of adverse
reactions declined progressively in the French trials, so that by day 14, reports
were rare except for reports of bleeding and spotting.

Table 3: Type of Reported Adverse Events Following Administration
of Mifepristone and Misoprostol in the U.S. and French Trials* (percentages)

U.S. Trials

French Trials

Abdominal Pain (cramping)

96

NA

Uterine cramping

NA

83

Nausea

61

43

Headache

31

2

Vomiting

26

18

Diarrhea

20

12

Dizziness

12

1

Fatigue

10

NA

Back pain

9

NA

Uterine hemorrhage

5

NA

Fever

4

NA

Viral infections

4

NA

Vaginitis

3

NA

Rigors (chills/shaking)

3

NA

Dyspepsia

3

NA

Insomnia

3

NA

Asthenia

2

1

Leg pain

2

NA

Anxiety

2

NA

Anemia

2

NA

Leukorrhea

2

NA

Sinusitis

2

NA

Syncope

1

NA

Endometritis/Salpingitis/Pelvic Inflammatory Disease

1

NA

Decrease in hemoglobin greater than 2 g/dL

NA

6

Pelvic pain

NA

2

Fainting

NA

2

*Only adverse reactions with incidence 1%
are included.

Postmarketing Experience

The following adverse reactions have also been reported during post-approval
use of Mifeprex and misoprostol. Because these reactions are reported voluntarily
from a population of uncertain size, it is not always possible to reliably estimate
their frequency or establish a causal relationship to drug exposure. No causal
relationship between these events and Mifeprex and misoprostol has been established:

DRUG INTERACTIONS

Although specific drug or food interactions with mifepristone have not been
studied, on the basis of this drug's metabolism by CYP 3A4, it is possible that
ketoconazole, itraconazole, erythromycin, and grapefruit juice may inhibit its
metabolism (increasing serum levels of mifepristone). Furthermore, rifampin,
dexamethasone, St. John's Wort, and certain anticonvulsants (phenytoin, phenobarbital,
carbamazepine) may induce mifepristone metabolism (lowering serum levels of
mifepristone).

Based on in vitro inhibition information, coadministration of mifepristone
may lead to an increase in serum levels of drugs that are CYP 3A4 substrates.
Due to the slow elimination of mifepristone from the body, such interaction
may be observed for a prolonged period after its administration. Therefore,
caution should be exercised when mifepristone is administered with drugs that
are CYP 3A4 substrates and have narrow therapeutic range, including some agents
used during general anesthesia.